麻豆传媒

NEW ORLEANS -- An investigational antibody targeting interleukin (IL)-31 in prurigo nodularis significantly reduced itch, skin lesions, and sleep disturbance in a phase III trial.

More than half of patients treated with nemolizumab met the primary endpoint of at least a 4-point improvement in the Peak Pruritus-Numerical Rating Scale (PP-NRS), and 38% met the endpoint of investigator global assessment (IGA) success after 16 weeks of treatment. Differences for both endpoints were approximately tripled versus a placebo group. More than twice as many patients in the nemolizumab arm had at least a 4-point improvement in sleep disturbance.

The type, frequency, and severity of treatment-emergent adverse events (TEAEs) were similar between the nemolizumab and placebo arms, reported Shawn Kwatra, MD, of Johns Hopkins Medicine in Baltimore, at the American Academy of Dermatology meeting.

"The improvements in pruritus, lesions, and sleep disturbance were observed as early as week 4," said Kwatra. "The results extend the efficacy and safety findings from the phase II study of nemolizumab in patients with prurigo nodularis."

During a discussion that followed his presentation, moderator Andrew Blauvelt, MD, of Oregon Medical Research Center in Portland, asked whether nemolizumab has the potential to "take away itch completely."

Kwatra said the ≥4-point improvement in PP-NRS has become the standard for clinical success, but "we can do better, so let's shift the goalposts. What you're going to see more often in the literature is 'relevant itch-free state,' which is the less-than 2 category. That's going to become a key secondary outcome. We don't have that data yet, but it's coming."

IL-31 is a key regulator of neuroinflammation and tissue fibrosis. A first-in-class monoclonal antibody, nemolizumab inhibits IL-31 binding to its receptor. The drug is being evaluated in several inflammatory skin conditions and has for atopic dermatitis.

A small randomized phase II trial showed that nemolizumab reduced baseline PP-NRS by 4.5 points (53% reduction) versus 1.7 points (20% reduction) in the placebo group. The results set the stage for OLYMPIA-2, which involved adults with prurigo nodularis duration of at least 6 months, PP-NRS ≥7, ≥20 nodules with bilateral distribution, and an IGA ≥3.

Patients were randomized 2:1 to nemolizumab every 4 weeks or placebo, and the primary endpoints were ≥4-point improvement in PP-NRS and IGA success (score of 0/1 and at least a 2-point improvement from baseline) after 16 weeks of treatment.

Data analysis included 274 patients (mean age 52.7 years), and 37% of the patients had more than 100 nodules. Other baseline characteristics were as follows: weekly PP-NRS (mean 8.4), IGA category 3 (56.9%) and 4 (43.1%), sleep disturbance score (7.2). About 80% of the patients had received prior topical therapy, 60% had received systemic therapy, and 5% had received intralesional corticosteroids.

The primary analysis showed an absolute difference of 35.4% for the PP-NRS endpoint (56.3% vs 20.9%) and a 26.7% difference for the IGA endpoint (37.7% vs 11.0%) in favor of nemolizumab (P<0.0001). The proportion of patients with at least a 4-point improvement in sleep disturbance was 51.9% in the nemolizumab arm and 20.9% in the placebo arm (P<0.0001).

"There is a rapid ascent [in nemolizumab activity] from baseline to week 4 in terms of patients who had a 4-point or greater improvement in itch," said Kwatra. "At week 4, after one injection, 41% of patients in the nemolizumab arm had a 4-point or greater reduction in itch compared to 7.7% of patients on placebo."

The impact on sleep disturbance and nodule count mirrored that for itch, showing rapid improvement following the first injection of nemolizumab, he added.

The most common adverse events in nemolizumab-treated patients were headache (6.6%), infection (5.5%), atopic dermatitis (5.5%), neurodermatitis (3.8%), and peripheral edema (3.3%).

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